RESUMO
Seprehvir (HSV1716) is an oncolytic herpes simplex virus-1 (HSV-1) previously demonstrated to be well tolerated in pediatric patients when administered intratumorally. To determine the safety of administering Seprehvir systemically, we conducted the first-in-human phase I trial of intravenous injection in young patients with relapsed or refractory extra-cranial solid cancers. We delivered a single dose of 5 × 104 infectious units (iu)/kg (maximum dose of 2 × 106) or 2.5 × 105 iu/kg (maximum dose of 1 × 107 iu) of Seprehvir via the peripheral vein, monitored adverse events, and measured tumor responses by imaging. We monitored HSV-1 serology as well as viremia and shedding by PCR and culture. We administered a single dose of Seprehvir to seven patients and multiple doses to two patients. We did not observe any dose-limiting toxicities. All five HSV-1 seronegative patients seroconverted by day 28. Four of nine patients had detectable HSV-1 genomes in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had stable disease in response to Seprehvir. Intravenous Seprehvir is well tolerated without viral shedding in children and young adults with late-stage cancer. Viremia consistent with virus replication holds promise for future Seprehvir studies at higher doses and/or in combination with other anti-neoplastic therapies.
Assuntos
Terapia Genética , Vetores Genéticos/genética , Herpesvirus Humano 1/genética , Neoplasias/terapia , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Administração Intravenosa , Adolescente , Adulto , Fatores Etários , Criança , Feminino , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Humanos , Masculino , Neoplasias/diagnóstico , Terapia Viral Oncolítica/efeitos adversos , Terapia Viral Oncolítica/métodos , Tomografia por Emissão de Pósitrons , Resultado do Tratamento , Adulto JovemRESUMO
Helcococcus ovis is a newly established species in the genus Helcococcus. The clinical significance of this organism in sheep has not been reported. In the current report, isolation of H. ovis from a 6-month-old mixed-breed ewe lamb that died of respiratory disease is described. Pathologic examination revealed severe, focally extensive, chronic necrotizing pleuritis with intralesional coccobacilli and mild, multifocal, subacute mucopurulent bronchopneumonia, indicating a bacterial etiology. A Gram-positive bacterium was isolated in heavy growth from the lung tissue. DNA sequence analysis on the 16S rDNA gene demonstrated that the isolate was H. ovis. To the authors' knowledge, this is the first report of isolation of H. ovis associated with infection in sheep with pleuritis and bronchopneumonia.